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BACKGROUND: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods. OBJECTIVES: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression. METHODS: In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort. RESULTS: Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001). CONCLUSIONS: The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients.

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Importance: There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial. Objective: To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis. Design, Settings and Participants: The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024. Exposure: Cohort-specific plasma lipoprotein(a) concentration tertiles. Main Outcomes and Measures: Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area. Results: Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% CI, 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma lipoprotein(a) concentrations were treated as a continuous variable. Conclusions and Relevance: In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.

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BACKGROUND: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. OBJECTIVES: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. METHODS: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. RESULTS: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. CONCLUSIONS: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

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BACKGROUND: Social isolation is associated with increased all-cause and premature mortality, poor chronic disease management, and mental health concerns. Limited research exists on interventions addressing social isolation among individuals under 65 despite its increasing prevalence among young and middle-aged adults. AIM: To identify interventions from the extant literature that address social isolation and loneliness in ambulatory healthcare settings in adults aged 18-64, and to identify elements of successful studies for future intervention design. DESIGN & SETTING: Systematic review of interventions targeting social isolation in community-dwelling adults aged 18-64 within ambulatory healthcare settings. METHOD: A search strategy was developed to identify relevant articles in the following databases: Ovid MEDLINE, Embase, EBM Reviews, Scopus, CINAHL and PsychInfo. Data were extracted on study design and setting, intervention type, outcome related to social isolation/loneliness and scale of measure used. RESULTS: 25,078 citations were identified and underwent title and abstract screening. 75 articles met our inclusion criteria and were synthesised, including an assessment of bias. Effective interventions were delivered in community health settings, incorporated a group component, and used digital technologies. They also addressed the association between mental health and social isolation using CBT approaches and enhanced self-management and coping strategies for chronic conditions through psycho-educational interventions. CONCLUSION: Future research should prioritise adults living in low- and middle-income countries, racialized individuals, as well as those with fewer educational opportunities. There is also a need to advance research in primary care settings, where longitudinal patient-provider relationships would facilitate the success of interventions.

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The UK Medical Research Council's widely used guidance for developing and evaluating complex interventions has been replaced by a new framework, commissioned jointly by the Medical Research Council and the National Institute for Health Research, which takes account of recent developments in theory and methods and the need to maximise the efficiency, use, and impact of research.

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This invited discussion paper highlights key updates in the MRC/NIHR's revised framework for the development and evaluation of complex nursing interventions and reflects on the implications for nursing research.

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BACKGROUND: A fairer economy is increasingly recognised as crucial for tackling widening social, economic and health inequalities within society. However, which actions have been evaluated for their impact on inclusive economy outcomes is yet unknown. OBJECTIVE: Identify the effects of political, economic and social exposures, interventions and policies on inclusive economy (IE) outcomes in high-income countries, by systematically reviewing the review-level evidence. METHODS: We conducted a review of reviews; searching databases (May 2020) EconLit, Web of Science, Sociological Abstracts, ASSIA, International Bibliography of the Social Sciences, Public Health Database, Embase and MEDLINE; and registries PROSPERO, Campbell Collaboration and EPPI Centre (February 2021) and grey literature (August/September 2020). We aimed to identify reviews which examined social, political and/or economic exposures, interventions and policies in relation to two IE outcome domains: (i) equitable distribution of the benefits of the economy and (ii) equitable access to the resources needed to participate in the economy. Reviews had to include primary studies which compared IE outcomes within or between groups. Quality was assessed using a modified version of AMSTAR-2 and data synthesised informed by SWiM principles. RESULTS: We identified 19 reviews for inclusion, most of which were low quality, as was the underlying primary evidence. Most reviews (n = 14) had outcomes relating to the benefits of the economy (rather than access to resources) and examined a limited set of interventions, primarily active labour market programmes and social security. There was limited high-quality review evidence to draw upon to identify effects on IE outcomes. Most reviews focused on disadvantaged groups and did not consider equity impacts. CONCLUSIONS: Review-level evidence is sparse and focuses on 'corrective' approaches. Future reviews should examine a diverse set of 'upstream' actions intended to be inclusive 'by design' and consider a wider range of outcomes, with particular attention to socioeconomic inequalities.

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Unemployment is more common among people living with HIV (PLWH) compared to the general population. PLWH who are employed have better physical and mental health outcomes compared to unemployed PLWH. The main objective of this mixed-methods study was to conduct a program evaluation of Employment Action (EACT), a community-based program that assists PLWH in Toronto, Ontario, Canada to maintain meaningful employment. We extracted quantitative data from two HIV services databases used by EACT, and collected qualitative data from 12 individuals who had been placed into paid employment through EACT. From 131 clients included in the analysis, 38.1% (n = 50) maintained their job for at least 6 weeks within the first year of enrollment in the EACT program. Gender, ethnicity, age, and first language did not predict employment maintenance. Our interviews highlighted the barriers and facilitators to effective service delivery. Key recommendations include implementing skills training, embedding PLWH as EACT staff, and following up with clients once they gain employment. Investment in social programs such as EACT are essential for strengthening their data collection capacity, active outreach to service users, and sufficient planning for the evaluation phase prior to program implementation.

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BACKGROUND: In May 2018, the Scottish Government set a minimum unit price (MUP) of £0·50 per unit of alcohol sold in Scotland to reduce alcohol-related health harms. We synthesised evidence to establish the effects of MUP on alcohol-related health and social harms, at population level and within specific societal groups. METHODS: We did a theory-based synthesis of academic and grey research evidence about impacts of MUP in Scotland, including compliance, price, consumption, health outcomes, social outcomes, public attitudes, and the alcoholic drinks industry. We searched the Public Health Scotland's MUP evaluation portfolio and relevant grey and academic literature for studies published between Jan 1, 2018, and Jan 31, 2023. We conducted systematic searches and screening of bibliographic databases (Scopus, Public Health Database, EconLit, MEDLINE, ProQuest Public Health, Social Policy and Practice, NHS Scotland Knowledge Network Library Search, medRxiv, bioRxiv, SSRN, Idox Knowledge Exchange, Social Policy & Practice, and Google Search). Search terms were tailored to specific databases but included variants of the terms "minimum unit pricing", "alcohol", and "policy". Eligibility literature included English-language research into impacts of MUP on either the population of Scotland or a specific subpopulation. We excluded conference abstracts, literature reviews, articles that did not report research, and research based solely on data from before the introduction of MUP. FINDINGS: We included 40 reports in our analysis. On the balance of evidence, MUP improved population-level health outcomes, demonstrated most starkly by a 13·4% reduction in alcohol-attributable deaths in Scotland compared with England. There was no evidence of substantial negative effects on the alcoholic drinks industry or social harms at the population level. While population-level outcomes were predominantly positive, some qualitative evidence suggests that MUP might have exacerbated health and social harms for some individuals or groups, especially those with alcohol dependence who were financially vulnerable. INTERPRETATION: MUP in Scotland has been effective in reducing alcohol-related health harms, with little evidence of any effect on social harms. If MUP continues, policymakers should consider raising the £0·50 per unit threshold and supplementing the intervention with policies or services to address any unintended negative effects experienced by specific groups. The synthesis is persuasive due to the prospective, theory-based design of the evaluation portfolio and the quality and comprehensiveness of the evidence. FUNDING: Scottish Government.

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BACKGROUND: Despite antiviral agents that can cure the disease, many individuals with Hepatitis C Virus (HCV) remain untreated. Primary care clinicians can play an important role in HCV treatment but often feel they do not have the requisite skills. METHODS: We implemented a population-based improvement intervention over 10 months to support treatment of HCV in a primary care setting. The intervention included a decision-support tool, education for clinicians, enhanced interprofessional team supports, mentorship, and proactive patient outreach. We used process and outcome measures to understand the impact on the proportion of patients who initiated treatment and achieved Sustained Virologic Response (SVR). We used physician focus groups and pharmacist interviews to understand the context and mechanisms influencing the impact of the intervention. RESULTS: Between December 2018 and June 2020, the percentage of HCV RNA positive patients who started treatment rose from 66.0% (354/536) to 75.5% (401/531) with 92.5% (371/401) of those starting treatment achieving SVR. Qualitative findings highlighted that the intervention helped raise awareness and confidence among physicians for treating HCV in primary care. A collaborative team environment, education, mentorship, and a decision-support tool integrated into the electronic record were all enablers of success although patient psychosocial complexity remained a barrier to engagement in treatment. CONCLUSION: A multifaceted primary care improvement initiative increased clinician confidence and was associated with an increase in the proportion of HCV RNA positive patients who initiated curative treatment.

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BACKGROUND: Employment is a key social determinant of health. People living with HIV (PLWH) have higher unemployment rates than the general population. Vocational rehabilitation services have been shown to have significant and positive impact on employment status for PLWH. Understanding whether integrating vocational rehabilitation with health care services is acceptable, from the perspectives of PLWH and their health care providers, is an area that is understudied. METHODS: We conducted a qualitative study and collected data from focus groups and interviews to understand the perspectives of stakeholders regarding the potential for vocational rehabilitation and health care integration. We completed five focus groups with 45 health care providers and one-to-one interviews with 23 PLWHs. Participants were sampled from infectious disease, primary care clinics, and AIDS Service Organizations in Toronto and Ottawa, Canada. Interviews were audio-recorded and transcribed. We conducted a reflexive thematic analysis of the transcripts. FINDINGS: We found health care providers have little experience assisting patients with employment and PLWH had little experience receiving employment interventions from their health care team. This lack of integration between health care and vocational services was related to uncertainties around drug coverage, physician role and living with an episodic disability. Health care providers thought that there is potential for a larger role for health care clinics in providing employment interventions for PLWH however patients were divided. Some PLWH suggest that health care providers could provide advice on the disclosure of status, work limitations and act as advocates with employers. INTERPRETATION: Health care providers and some PLWH recognize the importance of integrating health services with vocational services but both groups have little experience with implementing these types of interventions. Thus, there needs to be more study of such interventions, including the processes entailed and outcomes they aim to achieve.

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BACKGROUND: Artificial intelligence (AI) implementation in primary care is limited. Those set to be most impacted by AI technology in this setting should guide it's application. We organized a national deliberative dialogue with primary care stakeholders from across Canada to explore how they thought AI should be applied in primary care. METHODS: We conducted 12 virtual deliberative dialogues with participants from 8 Canadian provinces to identify shared priorities for applying AI in primary care. Dialogue data were thematically analyzed using interpretive description approaches. RESULTS: Participants thought that AI should first be applied to documentation, practice operations, and triage tasks, in hopes of improving efficiency while maintaining person-centered delivery, relationships, and access. They viewed complex AI-driven clinical decision support and proactive care tools as impactful but recognized potential risks. Appropriate training and implementation support were the most important external enablers of safe, effective, and patient-centered use of AI in primary care settings. INTERPRETATION: Our findings offer an agenda for the future application of AI in primary care grounded in the shared values of patients and providers. We propose that, from conception, AI developers work with primary care stakeholders as codesign partners, developing tools that respond to shared priorities.

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BACKGROUND: With large volumes of longitudinal data in electronic medical records from diverse patients, primary care is primed for disruption by artificial intelligence (AI) technology. With AI applications in primary care still at an early stage in Canada and most countries, there is a unique opportunity to engage key stakeholders in exploring how AI would be used and what implementation would look like. OBJECTIVE: To identify the barriers that patients, providers, and health leaders perceive in relation to implementing AI in primary care and strategies to overcome them. DESIGN: 12 virtual deliberative dialogues. Dialogue data were thematically analyzed using a combination of rapid ethnographic assessment and interpretive description techniques. SETTING: Virtual sessions. PARTICIPANTS: Participants from eight provinces in Canada, including 22 primary care service users, 21 interprofessional providers, and 5 health system leaders. RESULTS: The barriers that emerged from the deliberative dialogue sessions were grouped into four themes: (1) system and data readiness, (2) the potential for bias and inequity, (3) the regulation of AI and big data, and (4) the importance of people as technology enablers. Strategies to overcome the barriers in each of these themes were highlighted, where participatory co-design and iterative implementation were voiced most strongly by participants. LIMITATIONS: Only five health system leaders were included in the study and no self-identifying Indigenous people. This is a limitation as both groups may have provided unique perspectives to the study objective. CONCLUSIONS: These findings provide insight into the barriers and facilitators associated with implementing AI in primary care settings from different perspectives. This will be vital as decisions regarding the future of AI in this space is shaped.

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BACKGROUND: People experiencing homelessness are vulnerable to SARS-CoV-2 infection and its consequences. We aimed to understand the perspectives of people experiencing homelessness, and of the health care and shelter workers who cared for them, during the COVID-19 pandemic. METHODS: We conducted an interpretivist qualitative study in Toronto, Canada, from December 2020 to June 2021. Participants were people experiencing homelessness who received SARS-CoV-2 testing, health care workers and homeless shelter staff. We recruited participants via email, telephone or recruitment flyers. Using individual interviews conducted via telephone or video call, we explored the experiences of people who were homeless during the pandemic, their interaction with shelter and health care settings, and related system challenges. We analyzed the data using reflexive thematic analysis. RESULTS: Among 26 participants were 11 men experiencing homelessness (aged 28-68 yr), 9 health care workers (aged 33-59 yr), 4 health care leaders (aged 37-60 yr) and 2 shelter managers (aged 47-57 yr). We generated 3 main themes: navigating the unknown, wherein participants grappled with evolving public health guidelines that did not adequately account for homeless individuals; confronting placelessness, as people experiencing homelessness often had nowhere to go owing to public closures and lack of isolation options; and struggling with powerlessness, since people experiencing homelessness lacked agency in their placelessness, and health care and shelter workers lacked control in the care they could provide. INTERPRETATION: Reduced shelter capacity, public closures and lack of isolation options during the COVID-19 pandemic exacerbated the displacement of people experiencing homelessness and led to moral distress among providers. Planning for future pandemics must account for the unique needs of those experiencing homelessness.

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Among those visiting a testing centre in Toronto, ON, between March and April 2020, people experiencing homelessness (n = 214) were more likely to test positive for COVID-19 compared with those not experiencing homelessness (n = 1,836) even after adjustment for age, sex and medical co-morbidity (15.4% vs. 6.7%, p < 0.001; odds ratio [OR] 2.41, 95% confidence interval [CI: 1.51, 3.76], p < 0.001).

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